Iliopsoas abscess: Analysis and perspectives from an endemic region of Eastern Nepal

Abstract Objective: To evaluate the clinical profile and outcome in patients with iliopsoas abscess. Methods: A descriptive study was carried out in B.P. Koirala Institute of Health Science, Dharan, Nepal from February 2005 to March 2006. The medical records of all thirty six patients admitted in surgery ward with diagnosis of iliopsoas abscess during the study period were analyzed. Results: Thirty six patients were included the study. There were 22 (61.1%) males and 14 (38.9%) females with a mean age of 24.33 ±19.19 years. Demographic distribution of the patients revealed the highest number 13 (36.1%) from Sunsari district, eastern part of the country. Right sided unilateral involvement was the most common presentation and only 2 cases had bilateral involvement. In none of our patients the dorsolumbar spine radiograph revealed any involvement of the bone. The most common complaints were pain in lower abdomen and lump in iliac fossa with flexion deformity at hip joint. All the patients underwent open surgical drainage and their outcomes were analyzed in term of cure, morbidity and mortality. Staphylococcus aureus was the most common organism 24 (61.5%) isolated. Twenty two (91.66%) of Staphylococcus aureus samples were sensitive to ciprofloxacin. There was one mortality in the group who died of septicaemia secondary to necrotizing fascitis. Six patients had wound infection, which were cured by regular dressing. Conclusion: On the basis of our experience and review of available relevant literature, we can conclude that a high index of suspicion and awareness of the varying clinical picture are required to diagnose this condition properly. Ultrasonography should still be the preferred imaging modality as it is cheap, safe, cost effective and readily available. Ciprofloxacin should be used as a first line drug. Image guided aspiration may be practical in selected cases having little pus and traditional open drainage should be considered without hesitation

The burden of diseases and risk factors in Bangladesh, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: Bangladesh has made substantial progress in improving socioeconomic and health indicators over the past 50 years, but data on national disease burden are scarce. We used data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to estimate the burden of diseases and risk factors in Bangladesh from 1990 to 2019. / Methods: For this systematic analysis, we analysed data from vital registration systems, surveys, and censuses using multistage modelling processes to estimate life expectancy at birth, mortality rate, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs). Additionally, we compared the health status of Bangladesh with that of the other countries in the GBD south Asia region—Bhutan, India, Nepal, and Pakistan. / Findings: Life expectancy at birth in Bangladesh increased from 58·2 years (95% uncertainty interval 57·1–59·2) in 1990 to 74·6 years (72·4–76·7) in 2019. Between 1990 and 2019, the age-standardised mortality rate decreased from 1509·3 (1428·6–1592·1) to 714·4 (604·9–838·2) deaths per 100 000 population. In 2019, non-communicable diseases represented 14 of the top 20 causes of death; the leading three causes were stroke, ischaemic heart disease, and chronic obstructive pulmonary disease. High blood pressure, high fasting plasma glucose, and smoking were the top three risk factors. From 1990 to 2019, the rate of all-cause DALYs decreased by 54·9% (48·8–60·4). In 2019, the leading causes of DALYs and YLLs were neonatal disorders, stroke, and ischaemic heart disease, whereas musculoskeletal disorders, depressive disorders, and low back pain were the leading causes of YLDs. Bangladesh has the lowest age-standardised rates of mortality, YLDs, and YLLs and the highest life expectancy at birth in south Asia. / Interpretation: Over the past 30 years, mortality rates have reduced by more than half in Bangladesh. Bangladesh must now address the double burden of communicable and non-communicable diseases. Cost-effective, multisectoral efforts are needed to prevent and control non-communicable diseases, promote healthy lifestyles, and prevent premature mortality and disabilities. / Funding: Bill & Melinda Gates Foundation. / Translation: For the Bangla translation of the abstract see Supplementary Materials section

The E3 ligase HUWE1 inhibition as a therapeutic strategy to target MYC in multiple myeloma

Proteasome inhibitors have provided a significant advance in the treatment of multiple myeloma (MM). Consequently, there is increasing interest in developing strategies to target E3 ligases, de-ubiquitinases, and/or ubiquitin receptors within the ubiquitin proteasome pathway, with an aim to achieve more specificity and reduced side-effects. Previous studies have shown a role for the E3 ligase HUWE1 in modulating c-MYC, an oncogene frequently dysregulated in MM. Here we investigated HUWE1 in MM. We identified elevated expression of HUWE1 in MM compared with normal cells. Small molecule-mediated inhibition of HUWE1 resulted in growth arrest of MM cell lines without significantly effecting the growth of normal bone marrow cells, suggesting a favorable therapeutic index. Studies using a HUWE1 knockdown model showed similar growth inhibition. HUWE1 expression positively correlated with MYC expression in MM bone marrow cells and correspondingly, genetic knockdown and biochemical inhibition of HUWE1 reduced MYC expression in MM cell lines. Proteomic identification of HUWE1 substrates revealed a strong association of HUWE1 with metabolic processes in MM cells. Intracellular glutamine levels are decreased in the absence of HUWE1 and may contribute to MYC degradation. Finally, HUWE1 depletion in combination with lenalidomide resulted in synergistic anti-MM activity in both in vitro and in vivo models. Taken together, our data demonstrate an important role of HUWE1 in MM cell growth and provides preclinical rationale for therapeutic strategies targeting HUWE1 in MM

Genomewide Analyses Define Different Modes of Transcriptional Regulation by Peroxisome Proliferator-Activated Receptor-β/δ (PPARβ/δ)

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors with essential functions in lipid, glucose and energy homeostasis, cell differentiation, inflammation and metabolic disorders, and represent important drug targets. PPARs heterodimerize with retinoid X receptors (RXRs) and can form transcriptional activator or repressor complexes at specific DNA elements (PPREs). It is believed that the decision between repression and activation is generally governed by a ligand-mediated switch. We have performed genomewide analyses of agonist-treated and PPARβ/δ-depleted human myofibroblasts to test this hypothesis and to identify global principles of PPARβ/δ-mediated gene regulation. Chromatin immunoprecipitation sequencing (ChIP-Seq) of PPARβ/δ, H3K4me3 and RNA polymerase II enrichment sites combined with transcriptional profiling enabled the definition of 112 bona fide PPARβ/δ target genes showing either of three distinct types of transcriptional response: (I) ligand-independent repression by PPARβ/δ; (II) ligand-induced activation and/or derepression by PPARβ/δ; and (III) ligand-independent activation by PPARβ/δ. These data identify PPRE-mediated repression as a major mechanism of transcriptional regulation by PPARβ/δ, but, unexpectedly, also show that only a subset of repressed genes are activated by a ligand-mediated switch. Our results also suggest that the type of transcriptional response by a given target gene is connected to the structure of its associated PPRE(s) and the biological function of its encoded protein. These observations have important implications for understanding the regulatory PPAR network and PPARβ/δ ligand-based drugs

Sensing and Integration of Erk and PI3K Signals by Myc

The transcription factor Myc plays a central role in regulating cell-fate decisions, including proliferation, growth, and apoptosis. To maintain a normal cell physiology, it is critical that the control of Myc dynamics is precisely orchestrated. Recent studies suggest that such control of Myc can be achieved at the post-translational level via protein stability modulation. Myc is regulated by two Ras effector pathways: the extracellular signal-regulated kinase (Erk) and phosphatidylinositol 3-kinase (PI3K) pathways. To gain quantitative insight into Myc dynamics, we have developed a mathematical model to analyze post-translational regulation of Myc via sequential phosphorylation by Erk and PI3K. Our results suggest that Myc integrates Erk and PI3K signals to result in various cellular responses by differential stability control of Myc protein isoforms. Such signal integration confers a flexible dynamic range for the system output, governed by stability change. In addition, signal integration may require saturation of the input signals, leading to sensitive signal integration to the temporal features of the input signals, insensitive response to their amplitudes, and resistance to input fluctuations. We further propose that these characteristics of the protein stability control module in Myc may be commonly utilized in various cell types and classes of proteins

Disruption of Spectrin-Like Cytoskeleton in Differentiating Keratinocytes by PKCδ Activation Is Associated with Phosphorylated Adducin

Spectrin is a central component of the cytoskeletal protein network in a variety of erythroid and non-erythroid cells. In keratinocytes, this protein has been shown to be pericytoplasmic and plasma membrane associated, but its characteristics and function have not been established in these cells. Here we demonstrate that spectrin increases dramatically in amount and is assembled into the cytoskeleton during differentiation in mouse and human keratinocytes. The spectrin-like cytoskeleton was predominantly organized in the granular and cornified layers of the epidermis and disrupted by actin filament inhibitors, but not by anti-mitotic drugs. When the cytoskeleton was disrupted PKCδ was activated by phosphorylation on Thr505. Specific inhibition of PKCδ(Thr505) activation with rottlerin prevented disruption of the spectrin-like cytoskeleton and the associated morphological changes that accompany differentiation. Rottlerin also inhibited specific phosphorylation of the PKCδ substrate adducin, a cytoskeletal protein. Furthermore, knock-down of endogenous adducin affected not only expression of adducin, but also spectrin and PKCδ, and severely disrupted organization of the spectrin-like cytoskeleton and cytoskeletal distribution of both adducin and PKCδ. These results demonstrate that organization of a spectrin-like cytoskeleton is associated with keratinocytes differentiation, and disruption of this cytoskeleton is mediated by either PKCδ(Thr505) phosphorylation associated with phosphorylated adducin or due to reduction of endogenous adducin, which normally connects and stabilizes the spectrin-actin complex

Myc-regulated microRNAs attenuate embryonic stem cell differentiation

Myc proteins are known to have an important function in stem cell maintenance. As Myc has been shown earlier to regulate microRNAs (miRNAs) involved in proliferation, we sought to determine whether c-Myc also affects embryonic stem (ES) cell maintenance and differentiation through miRNAs. Using a quantitative primer-extension PCR assay we identified miRNAs, including, miR-141, miR-200, and miR-429 whose expression is regulated by c-Myc in ES cells, but not in the differentiated and tumourigenic derivatives of ES cells. Chromatin immunoprecipitation analyses indicate that in ES cells c-Myc binds proximal to genomic regions encoding the induced miRNAs. We used expression profiling and seed homology to identify genes specifically downregulated both by these miRNAs and by c-Myc. We further show that the introduction of c-Myc-induced miRNAs into murine ES cells significantly attenuates the downregulation of pluripotency markers on induction of differentiation after withdrawal of the ES cell maintenance factor LIF. In contrast, knockdown of the endogenous miRNAs accelerate differentiation. Our data show that in ES cells c-Myc acts, in part, through a subset of miRNAs to attenuate differentiation

Effect of 10% concentrations of salt, garlic and coriander on the quality of smoked Hilsa fish (Tenualosa ilisha)

The present study was conducted to evaluate the quality of smoked Hilsa fish (Tenualosa ilisha). The fishes were grouped into three parts. One part contains 10% salt, 10% garlic and 10% coriander and treated as Treatment 1 (T-l). Another named was Treatment 2 (T-2) and contained 10% salt and 10% garlic. The other parts contained 10% salt only and treated as Treatment 3 (T-3) to evaluate the quality of the smoked Hilsa with these ingredients for preparing a ready food item. All three treatments were found microbiologic ally acceptable since indicator organisms and Salmonella were not detected. However, from the results of overall acceptability, taste, colour and texture of the products, Treatment 2 had the best acceptance and significantly different when compared to the other treatments and selected the item as a quick but ready food item in laboratory condition. The moisture content, protein content, fat content, ash content, total volatile nitrogen and salt content of treatment 2 were found 39.65±0.19, 25.65±0.17, 24.85±0.17, 3.50±0.30, 2.55±0.22 and 16.20±0.14, respectively. All three treatments were found microbiologic ally acceptable since indicator organisms and Salmonella were not detected. However, from the results of overall acceptability, taste, colour and texture of the products, Treatment 2 had the best acceptance and significantly different when compared to the other treatment and selected the item as a quick but ready food item in laboratory condition. © 2012 Academic Journals Inc